Case Study 2: The TrovanTrial (trovafloxacin trial) (1996)

Case Study 2: The TrovanTrial (trovafloxacin trial) (1996)

In 1996 there was an epidemic outbreak of bacterial (meningococcal) meningitis in Tudun Wada, a very poor residential area in central Kano, Nigeria. The overpopulated and hot conditions in Tudun Wada were ideal for the spread of the infectious disease. A non-governmental organisation (NGO) called Médecins sans Frontières (MSF) assisted the government by providing free emergency treatment at the Infectious Diseases Hospital, a government hospital in Kano. In an effort to save as many lives as possible, the Nigerian government encouraged people of Kano through state radio announcements to take infected children to the government hospital in Kano for treatment. The people crowded the hospital. The epidemic swept through the poor communities leaving an estimated 15.000 people dead and thousands of children permanently disabled.

As the Nigerian government was battling to contain the epidemic with the help of the MSF, a team of researchers from a pharmaceutical company arrived in the country. They joined the government and the MSF at the government hospital in Kano. The researchers recruited approximately 200 children into a clinical trial for a medicine called trovafloxacin. This medicine had never been given to children by mouth (orally). The control group was given ceftriazone, an approved antibiotic for the treatment of bacterial meningitis. The government hospital, however, was using chloramphenicol to treat children presenting with bacterial meningitis.

There was wide-spread criticism about the trial. According to the families of the children participating to the trial:

  • Eleven children died: five of whom had taken trovafloxacin and six of whom had taken the lowered dose of ceftriaxone.

  • Many children were left blind, deaf, paralysed, or brain damaged. In response, the company argued that the bacterial meningitis epidemic had an overall mortality rate of 10 to 30% (this means that 10 to 30 patients in every 100 died from the condition). It was stated that trovafloxacin lowered the mortality rate to 6%, while chloramphenicol lowered the rate to 9.1%. The researchers are alleged to have left Kano once they had completed their studies in spite of the fact that the meningitis epidemic was still ravaging the community.

The main scientific rationale put forward by the company for testing trovafloxacinin in children was:

  • It is an oral antibiotic - this is an advantage compared to other medicines that are given intravenously.
  • Other similar medicines in the same antibiotic class of ‘fluoroquinolones’ had been successfully tested in children before.
  • Ciprofloxacin, a fluoroquinolone, was cited as an example that had been used in children without any serious side effects. However, ciprofloxacin was not tested in a disease outbreak.

The company argued that they could not obtain written informed consent because the parents and guardians were illiterate. As for ethical approval, the company claimed that the trial was approved by an ethics committee at Kano Hospital. They produced a letter to prove their claim, dated March 1996, a date when no ethics committee existed at Kano. The principal investigator later admitted that the approval letter was forged and back-dated to 28 March 1996, which was six days before the trovafloxacin trial started. They worked with a local Nigerian team of health personnel led by a local doctor who oversaw the trial at Kano.

The Nigerian government set up a committee of medical experts to investigate the circumstances surrounding the trial. The committee concluded that the medicine trial was illegal and unethical. In 2001, 30 Nigerian families who claim that trovafloxacin caused the deaths or permanent disability of their children as participants in the trial sued the company in a federal court in New York, US. They claimed that they had lost faith in the ability of the Nigerian legal process. The lawsuit was dismissed by a lower court but that decision was later reversed by a court of appeal. The case was settled in 2011 after a 15 year legal battle.

This case highlights a number of ethical issues, such as the voluntary nature of participation, the risk of exploitation of participants and their families and the informed consent and review process.